Handling the transfer of power: a note on the 1964 origins of the Douglas‐Home rules

Opposition is rarely a good preparation for government. The only post‐war government to enter office confident, well‐acquainted with the Civil Service and with a fund of administrative experience to draw on was the Attlee administration formed in 1945. The longer a party spends in opposition the more these assets disappear. Labour, by the end of the long period of Conservative rule in 1951–64, was largely unfamiliar with the burdens of office. This formed the background to the formulation of the Douglas‐Home rules, whereby informal contact is permitted between the Civil Service and the Opposition in advance of a general election. Since 1964 this arrangement has gradually become more extensive (especially after Neil Kinnock complained that the period for contact was too brief during the run‐up to the 1992 election) and more formalised. In late 1993 John Major agreed that contacts could be made from early 1996 in advance of the next election, rather than only during the last six months of a parliament, as had by then become the convention.’ The object of this short paper is, however, to explain how these rules originated.

Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure

The use of triple-therapy, pegylated-interferon, ribavirin and either of the first generation hepatitis C virus (HCV) protease inhibitors telaprevir or boceprevir, is the new standard of care for treating genotype 1 chronic HCV. Clinical trials have shown response rates of around 70–80%, but there is limited data from the use of this combination outside this setting. Through an expanded access programme, we treated 59 patients, treatment naïve and experienced, with triple therapy. Baseline factors predicting treatment response or failure during triple therapy phase were identified in 58 patients. Thirty seven (63.8%) of 58 patients had undetectable HCV RNA 12 weeks after the end of treatment. Genotype 1a (p = 0.053), null-response to previous treatment (p = 0.034), the rate of viral load decline after 12 weeks of previous interferon-based treatment (p = 0.033) were all associated with triple-therapy failure. The most common cause of on-treatment failure for telaprevir-based regimens was the development of resistance-associated variants (RAVs) at amino acids 36 and/or 155 of HCV protease (p = 0.027) whereas in boceprevir-based regimens mutations at amino acid 54 were significant (p = 0.015). SVR12 rates approaching 64% were achieved using triple therapy outside the clinical trial setting, in a patient cohort that included cirrhotics.